Responding to Light with Melanopsin

Certain mammalian retinal ganglion cells that express melanopsin act as photoreceptors that regulate circadian and pupillary responses. Although melanopsin is required for the photosensitivity of these cells, and has been proposed to act as a photopigment, its exact function has been uncertain. Two groups, Qiu et al. and Melyan et al., have now shown that heterologous expression of melanopsin conferred photosensitivity to mammalian cell lines. Qiu et al. expressed mouse melanopsin in human embryonic kidney 293 (HEK293) cells that stably expressed the receptor-operated cation channel TRPC3 and found that this led to light-evoked membrane potential depolarization, as well as light-evoked increases in free intracellular calcium. Light-evoked depolarization was blocked by internal application of GDPβS [an antagonist of heterotrimeric GTP-binding protein (G protein) signaling] or of a Gq/11 antagonist or by bath application of a phospholipase C antagonist. Experiments in which cells were exposed to light of different wavelengths indicated that the optimal wavelength was close to that for intrinsically photosensitive isolated rat retinal ganglion cells. Melyan et al. found that human melanopsin expressed in the Neuro-2a mouse neuroblastoma cell line enabled light-elicited inward currents in cells incubated with cis-isoforms of retinaldehyde. Experiments in which cells incubated with all-trans-retinaldehyde were pre-exposed to light outside the wavelength that elicited currents suggested that melanopsin could also act as a photoisomerase. Pharmacological analysis implicated G proteins, intracellular calcium mobilization, and cyclic GMP in the response of the Neuro-2a cells to light. Thus, research from both groups points to a role for melanopsin as a functional photopigment.